CSHL Cancer Center ? Overall Project Summary/Abstract The Cold Spring Harbor Laboratory (CSHL) Cancer Center is a premier cancer research center that uses innovative and collaborative approaches to address some of the most pressing challenges facing cancer biologists and cancer patients today. In particular, research in CSHL Cancer Center is focused on two primary problems: improving cancer diagnostics and increasing therapeutic effectiveness. Researchers in the CSHL Cancer Center are employing cutting edge genetic and genomic approaches to molecularly characterize cancer. The goals of this research are to both develop new diagnostic tools and to also define cancer subtypes so that clinicians will be able to select the most effective therapeutic approaches. CSHL Cancer Center researchers are at the forefront of developing and applying these genomic approaches; discoveries like single cell sequencing have the power to revolutionize diagnostics and are already demonstrating tremendous potential in the clinic. The CSHL Cancer Center is building upon its outstanding foundation in basic discovery science to identify and develop new therapeutic targets for multiple tumor types. More than ten years ago, the Cancer Center formalized this strategy with the creation of a ?cancer discovery pipeline.? The plan integrated basic cancer biology, human cancer genetics, high-throughput screening technology, and innovative animal models in an effort to improve existing treatments for cancer. This pipeline has been tremendously successful. Cancer Center researchers have discovered new cancer genes, identified potential therapeutic targets, and explored new drug resistance mechanisms. As this basic research continues, the Cancer Center is aiming to extend the pipeline even further into translational research. Over the next five years, as part of a Cancer Therapeutics Initiative, the Cancer Center will bring its basic research discoveries to preclinical and clinical settings. Funding from the National Cancer Institute provides the CSHL Cancer Center with the organizational and financial support needed to make a significant impact on cancer diagnosis and treatment. The three research programs (Gene Regulation & Cell Proliferation; Signal Transduction; Cancer Genetics) provide opportunities for members to come together, maximizing collaboration and communication. The nine Shared Resources provide access to technologies, services, and expertise to enhance productivity and promote multidisciplinary interactions. Essential Developmental Funds enable the Center to remain at the forefront of cancer research. Together, these elements of the CSHL Cancer Center create an environment that supports the level of scientific discovery required to make real progress in improving cancer diagnosis and treatment.